Trial Outcomes & Findings for A Study of Guselkumab Subcutaneous Therapy in Participants With Moderately to Severely Active Crohn's Disease (NCT NCT05197049)

NCT ID: NCT05197049

Last Updated: 2025-11-13

Results Overview

Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) and a decrease in total CDAI score over time indicates improvement in disease activity.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

350 participants

Primary outcome timeframe

At Week 12

Results posted on

2025-11-13

Participant Flow

Out of 350 participants randomized (1:1:1) to 1 of 3 treatments, 3 participants were excluded from all analysis sets due to non-compliance with Good Clinical Practice (GCP) guidance at 1 study site. Hence 347 participants were included in full analysis set. Study included a 24 week (wk) main treatment (12-wk induction followed by 12-wk maintenance) period followed by extension treatment period. In extension period, participants continued same maintenance dose regimen they received at Week 24.

Results through the Week 48 visit (cutoff date of 01 March 2024) are reported. Results of remaining duration of the study will be reported after study completion.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg SC injection on Weeks 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 100 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48 and a placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment (sham): continued receiving guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 400 mg SC injection on Weeks 16, 20 and 24, and placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.
Overall Study STARTED	118	117	115
Overall Study Treated	117	115	115
Overall Study Participants Who Met at Least 1 Rescue Criteria at Week 16	44	14	14
Overall Study COMPLETED	99	110	114
Overall Study NOT COMPLETED	19	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg SC injection on Weeks 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 100 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48 and a placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment (sham): continued receiving guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 400 mg SC injection on Weeks 16, 20 and 24, and placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	3	1	0
Overall Study Withdrawal by Subject	15	3	1
Overall Study GCP non-compliance	1	2	0

Baseline Characteristics

A Study of Guselkumab Subcutaneous Therapy in Participants With Moderately to Severely Active Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 100 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48 and a placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment (sham): continued receiving guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 400 mg SC injection on Weeks 16, 20 and 24, and placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 28 through Week 48.	Guselkumab 400 mg + 200 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Total n=347 Participants Total of all reporting groups
Region of Enrollment CROATIA	0 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants
Age, Categorical <=18 years	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants
Age, Categorical Between 18 and 65 years	114 Participants n=10 Participants	113 Participants n=10 Participants	111 Participants n=20 Participants	338 Participants n=45 Participants
Age, Categorical >=65 years	3 Participants n=10 Participants	2 Participants n=10 Participants	4 Participants n=20 Participants	9 Participants n=45 Participants
Sex: Female, Male Female	50 Participants n=10 Participants	49 Participants n=10 Participants	45 Participants n=20 Participants	144 Participants n=45 Participants
Sex: Female, Male Male	67 Participants n=10 Participants	66 Participants n=10 Participants	70 Participants n=20 Participants	203 Participants n=45 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=10 Participants	10 Participants n=10 Participants	8 Participants n=20 Participants	27 Participants n=45 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	93 Participants n=10 Participants	94 Participants n=10 Participants	98 Participants n=20 Participants	285 Participants n=45 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=10 Participants	11 Participants n=10 Participants	9 Participants n=20 Participants	35 Participants n=45 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants
Race (NIH/OMB) Asian	28 Participants n=10 Participants	26 Participants n=10 Participants	22 Participants n=20 Participants	76 Participants n=45 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants
Race (NIH/OMB) Black or African American	5 Participants n=10 Participants	0 Participants n=10 Participants	4 Participants n=20 Participants	9 Participants n=45 Participants
Race (NIH/OMB) White	71 Participants n=10 Participants	79 Participants n=10 Participants	79 Participants n=20 Participants	229 Participants n=45 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=10 Participants	10 Participants n=10 Participants	10 Participants n=20 Participants	33 Participants n=45 Participants
Region of Enrollment BELGIUM	1 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants
Region of Enrollment Bosnia	3 Participants n=10 Participants	4 Participants n=10 Participants	4 Participants n=20 Participants	11 Participants n=45 Participants
Region of Enrollment BRAZIL	13 Participants n=10 Participants	12 Participants n=10 Participants	7 Participants n=20 Participants	32 Participants n=45 Participants
Region of Enrollment CHINA	19 Participants n=10 Participants	16 Participants n=10 Participants	16 Participants n=20 Participants	51 Participants n=45 Participants
Region of Enrollment CZECH REPUBLIC	5 Participants n=10 Participants	7 Participants n=10 Participants	2 Participants n=20 Participants	14 Participants n=45 Participants
Region of Enrollment FRANCE	5 Participants n=10 Participants	3 Participants n=10 Participants	3 Participants n=20 Participants	11 Participants n=45 Participants
Region of Enrollment GERMANY	4 Participants n=10 Participants	8 Participants n=10 Participants	1 Participants n=20 Participants	13 Participants n=45 Participants
Region of Enrollment HUNGARY	4 Participants n=10 Participants	3 Participants n=10 Participants	3 Participants n=20 Participants	10 Participants n=45 Participants
Region of Enrollment ISRAEL	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	1 Participants n=45 Participants
Region of Enrollment ITALY	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants
Region of Enrollment JAPAN	5 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	6 Participants n=45 Participants
Region of Enrollment JORDAN	15 Participants n=10 Participants	8 Participants n=10 Participants	9 Participants n=20 Participants	32 Participants n=45 Participants
Region of Enrollment LITHUANIA	1 Participants n=10 Participants	0 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants
Region of Enrollment MALAYSIA	0 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants
Region of Enrollment NEW ZEALAND	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants
Region of Enrollment POLAND	27 Participants n=10 Participants	28 Participants n=10 Participants	33 Participants n=20 Participants	88 Participants n=45 Participants
Region of Enrollment SLOVAKIA	1 Participants n=10 Participants	4 Participants n=10 Participants	4 Participants n=20 Participants	9 Participants n=45 Participants
Region of Enrollment SOUTH KOREA	2 Participants n=10 Participants	6 Participants n=10 Participants	3 Participants n=20 Participants	11 Participants n=45 Participants
Region of Enrollment SPAIN	1 Participants n=10 Participants	3 Participants n=10 Participants	1 Participants n=20 Participants	5 Participants n=45 Participants
Region of Enrollment TAIWAN	2 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	3 Participants n=45 Participants
Region of Enrollment TURKEY	1 Participants n=10 Participants	3 Participants n=10 Participants	1 Participants n=20 Participants	5 Participants n=45 Participants
Region of Enrollment UNITED STATES	8 Participants n=10 Participants	5 Participants n=10 Participants	17 Participants n=20 Participants	30 Participants n=45 Participants
AgeContinuous	36 years STANDARD_DEVIATION 12.71 • n=10 Participants	37.4 years STANDARD_DEVIATION 13.32 • n=10 Participants	39.1 years STANDARD_DEVIATION 12.56 • n=20 Participants	37.5 years STANDARD_DEVIATION 12.89 • n=45 Participants

PRIMARY outcome

Timeframe: At Week 12

Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study intervention. As prespecified in Statistical Analysis Plan (SAP), for this outcome measure (OM), combined data for both guselkumab treatment groups were collected and analyzed because they received the same regimen of guselkumab 400 mg SC at Weeks 0, 4, and 8.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=230 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants Who Achieved Clinical Remission at Week 12	21.4 Percentage of participants Interval 13.9 to 28.8	56.1 Percentage of participants Interval 49.7 to 62.5	—	—

PRIMARY outcome

Timeframe: At Week 12

Percentage of participants who achieved endoscopic response at Week 12 were reported. Endoscopic response was defined as greater than or equal to (\>=) 50 percent (%) improvement from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) score. SES-CD evaluated 4 endoscopic components (presence and size of ulcer, extent of ulcerated surface, extent of affected surface, and presence and type of narrowing) across 5 ileocolonic segments (ileum, right colon, transverse colon, left colon, and rectum), each scored from 0 (best) to 3 (worst) for each segment except narrowing component for which the maximum total score (that is, stricturing) was 11 points. The total SES-CD score was the sum of all the component scores across all the segments and it ranged from 0 (best) to 56 (worst), where higher scores indicated more severe disease.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=230 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants Who Achieved Endoscopic Response at Week 12	21.4 Percentage of participants Interval 13.9 to 28.8	41.3 Percentage of participants Interval 34.9 to 47.7	—	—

SECONDARY outcome

Timeframe: At Week 24

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study intervention.

Percentage of participants who achieved clinical remission at Week 24 were reported. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) and a decrease in total CDAI score over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=115 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants Who Achieved Clinical Remission at Week 24	21.4 Percentage of participants Interval 13.9 to 28.8	60.9 Percentage of participants Interval 51.9 to 69.8	58.3 Percentage of participants Interval 49.2 to 67.3	—

SECONDARY outcome

Timeframe: At Week 12

Percentage of participants who achieved PRO-2 remission at Week 12 were reported. PRO-2 remission was defined as an abdominal pain (AP) mean daily score \<=1, and stool frequency (SF) mean daily score \<=3, and no worsening of AP or SF from baseline. Mean daily AP score based on the CDAI was defined as the sum of abdominal pain/cramps ratings in the previous 7 days in a diary card divided by the total number of days assessments were performed. Average daily SF score based on the CDAI was defined as the sum of number of liquid or very soft stools in the previous 7 days in a diary card divided by the total number of days assessments were performed. Mean daily SF and AP scores at a scheduled visit were not calculated if total number of days of assessment was less than 5. Higher PRO-2 scores indicated more severe disease.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=230 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants Who Achieved Patient-reported Outcome (PRO)-2 Remission at Week 12	17.1 Percentage of participants Interval 10.3 to 23.9	49.1 Percentage of participants Interval 42.7 to 55.6	—	—

SECONDARY outcome

Timeframe: At Week 12

Clinical response was defined as a decrease from baseline in CDAI score \>= 100 points or CDAI score \< 150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) and a decrease in total CDAI score over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=230 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants Who Achieved Clinical Response at Week 12	33.3 Percentage of participants Interval 24.8 to 41.9	73.5 Percentage of participants Interval 67.8 to 79.2	—	—

SECONDARY outcome

Timeframe: Placebo, Guselkumab 400 mg + 100 mg, and Guselkumab 400 mg + 200 mg: From Week 0 up to Week 48; Placebo arm subset - Rescue Treatment: From Week 16 up to Week 48

Population: Safety analysis set included all randomized participants who received at least 1 dose of study intervention.

Percentage of participants with TEAEs through Week 48 were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant participating in a clinical study and does not necessarily have a causal relationship with the study drug. An AE that occurred at or after the initial administration of study drug (Week 0) through data cutoff of Week 48 was considered treatment-emergent.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=115 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab n=44 Participants Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Through Week 48	65.8 Percentage of participants	82.6 Percentage of participants	80.0 Percentage of participants	75.0 Percentage of participants

SECONDARY outcome

Timeframe: Placebo, Guselkumab 400 mg + 100 mg, and Guselkumab 400 mg + 200 mg: From Week 0 up to Week 48; Placebo arm subset - Rescue Treatment: From Week 16 up to Week 48

Population: Safety analysis set included all randomized participants who received at least 1 dose of study intervention.

Percentage of participants with TESAEs through Week 48 were reported. An SAE was any untoward medical occurrence in a clinical study participant resulting in any of the following outcomes or was deemed significant for any other reason: death, life-threatening (immediate risk of dying), initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect. An AE does not necessarily have a causal relationship with the study drug. Any SAE that occurred at or after the initial administration of study drug (Week 0) through the data cutoff of Week 48 was considered treatment-emergent.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=115 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab n=44 Participants Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through Week 48	13.7 Percentage of participants	13.0 Percentage of participants	7.8 Percentage of participants	2.3 Percentage of participants

SECONDARY outcome

Timeframe: Placebo, Guselkumab 400 mg + 100 mg, and Guselkumab 400 mg + 200 mg: From Week 0 up to Week 48; Placebo arm subset - Rescue Treatment: From Week 16 up to Week 48

Population: Safety analysis set included all randomized participants who received at least 1 dose of study intervention.

Percentage of participants with TEAEs leading to discontinuation of study drug through Week 48 were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant participating in a clinical study and does not necessarily have a causal relationship with the study drug. An AE that occurred at or after the initial administration of study drug (Week 0) through data cutoff of Week 48 was considered treatment-emergent.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Participants received placebo matched to guselkumab 400 milligrams (mg) subcutaneous (SC) injection at Weeks 0, 4, and 8 followed by placebo matched to guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (Crohn's Disease Activity Index \[CDAI\] score greater than \[\>\] 220 and less than \[\<\] 70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50 percent \[%\] increase in Simple Endoscopic Score for Crohn's Disease \[SES-CD\] from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48.	Combined: Guselkumab 400 mg n=115 Participants Participants of arm "Guselkumab 400 mg + 100 mg" and "Guselkumab 400 mg + 200 mg" received guselkumab 400 mg SC injections at Week 0, 4, and 8.	Guselkumab 400 mg + 200 mg n=115 Participants Participants received guselkumab 400 mg SC injection at Weeks 0, 4, and 8, followed by guselkumab 200 mg SC injection every 4 weeks from Week 12 through Week 48, and a placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48. Participants who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: (sham): continued receiving guselkumab 200 mg SC injection every 4 weeks from Week 16 through Week 48, along with placebo matched to guselkumab 200 mg SC injection on Weeks 16, 20 and 24 and placebo matched to guselkumab 100 mg SC injection every 8 weeks from Week 16 through Week 48.	Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab n=44 Participants Participants randomized to placebo arm who met at least one of the rescue criteria (CDAI score \>220 and \<70-point reduction from baseline CDAI score at both Weeks 12 and 16 or at least 50% increase in SES-CD from baseline at Week 12) at Week 16 received rescue treatment: guselkumab 400 mg SC injection at Weeks 16, 20, and 24 along with placebo matched to guselkumab 100 mg on Week 16 and 24 followed by guselkumab 100 mg SC injection every 8 weeks from Week 32 through Week 48 and placebo matched to guselkumab 200 mg every 4 weeks from Week 28 through Week 48. For this arm, data were collected and analyzed after the participants of arm "Placebo" crossed over to receive rescue treatment with guselkumab.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation of Study Drug Through Week 48	8.5 Percentage of participants	3.5 Percentage of participants	2.6 Percentage of participants	2.3 Percentage of participants

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo Arm Subset (Rescue Treatment): Placebo to Guselkumab

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Guselkumab 400 mg + 100 mg

Serious events: 15 serious events

Other events: 65 other events

Deaths: 1 deaths

Guselkumab 400 mg + 200 mg

Serious events: 9 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Medical Leader IMM

Janssen-Cilag International NV

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER